Endothelin Receptor Function and Acute Stress (End-Stress)

Endothelin Receptor Function and Acute Stress (End-Stress)

Our bodies respond differently to stress. Animal studies by the investigators have found that endothelin-1 plays a role in regulating blood pressure in response to stress. This study is an extension of the investigators previous animal work to evaluate the role of endothelin-1 during stress in humans.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension
• Intervention / Treatment: Drug: Bosentan; Drug: Placebo

Detailed Description

Using a salt sensitive animal model of prehypertension, the Dahl S rat,the investigators have previously published that acute stress elicits a pressor response that is accompanied by an increase in 8 isoprostane and endothelin-1. However, the pressor response is suppressed by endothelin A/B receptor antagonism. Moreover, the investigators have identified that the increase in 8-isoprostane occurs downstream of endothelin receptor activation. These data indicate that endothelin receptor activation is a main player In the pressor response to acute stress in pre-hypertensive animals; however, this phenomenon has yet to be elucidated in humans.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and premenopausal women (Ages 18-50 years old)
• Self-reported Black and White adults
• Lean adults (BMl <25 kg/m^)
• Obese adults (BMl > 30 kg/m^)

Exclusion Criteria:

• Having a BMI less than 16 kg/m2 (severely and very severely underweight) or that is greater than 40 kg/m2 (Class III obesity)
• Having evidence of cardiovascular, pulmonary, renal, hepatic, cerebral, or metabolic disease
• Having evidence of pregnancy
• Using medications that affect vascular tone (i.e., nitrates, etc.)
• Postmenopausal women
• Uncontrolled hypertension
• Individuals who are on a restricted salt diet
• Having a history of chronic pain
• Having a history of rheumatoid arthritis
• Using medications that are contraindicated with bosentan (i.e. glyburide, cyclosporine)
• Liver dysfunction (which may be identified with the blood sample we take)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bosentan; Sub-Chronic (3 days) Bosentan 250mg/day.	Drug: Bosentan; Stress response and vascular function will be assessed 3 days following 125 mg twice per day of Bosentan; Other Names: Tracleer
Placebo Comparator: Placebo; Stress response and endothelial function will be determined following a three day treatment of placebo	Drug: Placebo; Stress response and vascular function will be assessed 3 days following twice per day placebo; Other Names: lactose capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-Mediated Dilation (FMD)	Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function.	Baseline and 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial Stiffness Evaluation (PWV)	A tonometer will be gently applied on the carotid artery and then the femoral artery and the radial artery to record how fast blood flows between each of the points.	Baseline and 3 days
Physio Flow	Six surface electrodes will be placed on the body. 2 on the neck, 2 on the chest, and 2 on the back in order to measure parameters of the heart during exercise.	Baseline and 3 days
Femoral blood flow	Though ultrasound assessment; resistance of the blood flow, blood flow, blood velocity, and arterial diameter will all be measured in the femoral artery during the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes.	Baseline and 3 days
Blood Pressure	Blood pressure will measured in response to the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes.	Baseline and 3 days
Resting Energy Expenditure	REE will be assessed before and following treatment	Baseline and 3 days

Collaborators and Investigators

• Sponsor: Augusta University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Ryan Harris, Ph.D., Augusta University

Publications and helpful links

Helpful Links

• Laboratory of Integrative Vascular and Exercise Physiology

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: April 14, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (Estimated): April 16, 2014

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: stress; Bosentan; blood pressure; inflammation; oxidative stress; BMI; pulse wave velocity; flow-mediated dilation; endothelial function; arterial stiffness; Nitric Oxide; Endothelin-1; Cold Pressor Test; physio flow; Endothelin Receptor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: End-Stress; 5P01HL069999 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES